Certain thienyl aliphatic hydrocarbon amides

ABSTRACT

A novel fatty acid amide useful as an anti-arteriosclerotic agent which is represented by the formula, WHEREIN R represents a saturated or unsaturated straight or branched aliphatic hydrocarbon group having 15 to 25 carbon atoms which may bear a hydroxyl group, A represents a lower alkyl group, aryl group or aralkyl group and B represents a heterocyclic radical containing a nitrogen, oxygen or sulfur atom, such as, for example, Alpha -(thienyl or pyridyl)-ethyl or benzyl amide of linoleic acid, isostearic acid, linolenic acid, oleic acid or safflower oil. These compounds are prepared by reacting the appropriate fatty acid or reactive derivative with an amine of the formula, These compounds may be incorporated in foodstuffs or ingested with a suitable carrier.

United States Patent Suzuki et al.

[54] CERTAIN THIENYL ALIPHATIC HYDROCARBON AMIDES [72] Inventors: Yoshio Suzuki, Amagasaki-shi; Shunji Aono, Toyonaka-shi; I-Iideaki Fukushima, Nishinomiya-shi, all of Japan Sumitomo Chemical Company, Ltd., Higashi-ku, Osaka, Japan [22] Filed: Aug. 29, 1969 [21] Appl. No.: 854,308

[73] Assignee:

[30] Foreign Application Priority Data Sept. 7, 1968 Japan ..43/64394 [52] US. Cl ..260/332.2 A, 260/295 AM, 260/2955 A,

[5 1] Int. Cl. ..C07d 63/10 [58] Field of Search ..260/332.2 R, 295 AM, 295.5 AM

[56] References Cited UNITED STATES PATENTS 3,555,035 1/1971 Meisels et al. ..260/295 OTHER PUBLICATIONS Roberts et al., Basic Principles of Organic Chemistry Benjamin Inc., page 531 (I965).

[ 51 May 30,1972

Primary Examiner-Alan L. Rotman Attorney-Stevens, Davis, Miller & Mosher [57] ABSTRACT A novel fatty acid amide useful as an anti-arteriosclerotic agent which is represented by the formula,

A RCONHC These compounds may be incorporated in foodstuffs or ingested with a suitable carrier.

8 Claims, No Drawings CERTAIN THIENYL ALIPHATIC HYDROCARBON AMIDES This invention relates to novel anti-arteriosclerotic agents. More particularly, the invention pertains to novel agents which are useful for the lowering of elevated levels of cholesterol in the blood.

Arteriosclerosis is an adult disease for which there is no known satisfactory cure. Although the cause for arteriosclerosis is not yet known in spite of discussions in the academic circles, it has broadly been recognized that one of the most significant histo-pathological manifestations of arteriosclerosis is the deposition of lipids in the blood. Accordingly, research has been directed to the disturbed metabolism of lipids, and attention has been given to the extraordinarily elevated level of cholesterol in the blood.

A number of experimental and clinical facts have been reported, which indicate the relationship between arteriosclerosis and elevated blood cholesterol level. Hence, the development of agents to reduce the elevated blood cholesterol level is considered extremely important for the prevention of arteriosclerosis.

Concentrated efi'orts have heretofore been made for the development of such agents for lowering cholesterol, and a number of compounds have been tested clinically, but none of them have been proved to be completely satisfactory. Some of them are fairly effective but produce significantly harmful side effects, and others have inadequate effectiveness, so that they are required to be administered in large doses.

A group of compounds practically employed nowadays for the above purpose comprises unsaturated fatty acids, especially linoleic acid. The reason why linoleic acid is employed is because of its harmlessness to the human body. However, its effectiveness is not very high, and is uncertain and indefinite. Accordingly, large doses are required to obtain at least appreciable efficacy as a cholesterol-lowering agent.

The present inventors have found a group of compounds which are effective as cholesterol-lowering agents and are sub stantially nontoxic.

It is therefore an object of the present invention to provide cholesterol-lowering agents.

Another object is to provide a process for preparing cholesterol-lowering agents.

A further object is to provide pharmaceutical compositions containing such agents.

Other objects will be apparent from the following description.

In order to accomplish the above objects, the present invention provides fatty acid amides represented by the formula,

A R C ONH C H wherein R represents a saturated or unsaturated aliphatic hydrocarbon group having to 25 carbon atoms and which may bear a hydroxyl group, A represents a lower alkyl group, monocyelic aryl group or monocyclic aralkyl group, and B represents a hetero-cyclic radical containing a nitrogen, oxygen or sulfur atom as the hetero atom, and a process for the production of the same.

These fatty acid amides (l) are novel compounds, and are prepared by reacting a fatty acid represented by the formula,

R-COOH ([1) wherein R is as defined above, its reactive derivative or a natural oil containing the fatty acid, with an amine represented by the formula,

wherein A and B are as defined above.

Examples of the fatty acids represented by the general formula (ll), the reactive derivatives thereof, and the natural oils which are used in the present invention include the following:

Saturated fatty acids palmitic acid, stearic acid, isostearic acid, arachic acid, behenic acid, lignoceric acid, pentacosanoic acid, hexacosanoic acid, and the like.

Unsaturated fatty acids palmit-oleic acid, zoomaric acid, oleic acid, petroselinic acid, elaidic acid, vaccenic acid, gadoleic acid, erucic acid, brassidic acid, selacholeic acid, linoleic acid, linolenic acid, linoelaidic acid, ricinoleic acid, eleosostearic acid, parinaric acid, ylinolenic acid, eicosatetraenoic acid, eicosahexaenoic acid, arachidonic acid and the like.

Reactive derivatives an acid halide, acid anhydride, mixed acid anhydride, lower alkyl ester and glyceride, and the like of the foregoing saturated and unsaturated fatty acids.

Natural oils hempseed oil, linseed oil, perilla oil, oiticica oil, kaya oil, walnut oil, poppyseed oil, safflower oil, watermelon-seed oil, soybean oil, sunflower oil, rice bran oil, pumpkin-seed oil, kaoliang oil, sesame oil, corn oil, maize oil, rape seed oil, cottonseed oil, olive oil, cashew oil, tsubaki oil, ergot oil, caster oil, peanut oil, palm oil, palm kernel oil, coconut oil, beef tallow, lard, bone oil, horse fat, locust oil, chrysalis oil, shark oil, cuttlefish oil, sardine oil, mackerel oil, saury oil, herring oil, saurel oil, cod oil, trout oil, grey mullet oil, tunny oil, menuke oil, menhaden oil, eel oil, flatfish oil, whale oil, liver oil, and residual oil.

The alkyl group of A of the amine derivative (Ill) used in the present invention is a straight or branched alkyl group having one to four carbon atoms. Examples of the aralkyl of A of the amine derivative ([11) include benzyl group, phenylethyl group, phenylpropyl group, and phenylbutyl group. Preferred examples of the hetero-cyclic compound radical of B of the amine derivative (Ill) contain four to five carbon atoms and include pyrrolyl group, pyrrolinyl group, pyrrolidinyl group, pyridyl group, piperidyl group, morpholinyl group, furyl group, hydrofuryl group, pyrryl group, hydro-pyrryl group, thienyl group, hydrothienyl group, and the like.

Amine derivatives used in the present invention can be produced according to methods disclosed in, for example, J. Amer. Chem. Soc., 64, 477 (1942), ibid, 50, 2484 (1928), J. Org. Chem., 23, 989 1959) or ibid, 24, 1936 (1959).

In accordance with the present invention, the desired fatty acid amides can be obtained with advantages by the following reaction procedures:

1. reaction of a fatty acid with an amine in the presence or absence of a dehydrating agent to remove water,

2. reaction of a fatty acid ester or glyceride with an amine in the presence or absence of a catalyst to remove alcohol,

3. reaction of a fatty acid halide with an amine, or

4. reaction of an acid anhydride or a mixed acid anhydride with an amine.

The above-mentioned reaction procedures will be successively explained in further detail below.

1. Reaction of the fatty acid with the amine:

In this reaction, the two compounds are used in equimolar amounts, or either one of them is used in excess. In the case of the absence of dehydrating agent, a solvent such as toluene or xylene may be used, if necessary. Ordinarily, the reaction is carried out at l0O-300 C in the absence of solvent, while removing or not removing eliminated water. The reaction is usually completed in several hours to several days. The starting material used in excess is recovered and is reused in the reaction, whereby the desired fatty acid amide can be synthesized economically. Further in the case of the presence of a dehydrating agent, the two compounds are used in equimolar amounts or either one of them is used in excess, and the two are dissolved in a suitable solvent, e.g. benzene, toluene, xylene, carbon tetrachloride-or the like. To this solution is added a dehydrating agent selected from the group consisting acid, p-toluenesulfonic acid, p-toluenesulfonyl chloride, and acidic and basic ion exchange resins, e.g., Amberlite IRA-400, lR-50, and lR-120, and Amberlyst 15, 21, 26, and 27 (all these are trade names of ion exchange resins produced by Rohm & Haas Co.). Subsequently, the mixture is refluxed for 10 to 200 hours while removing water formed during the reaction using a water-separator, if necessary. Thereafter, the dehydrating agent is removed, and then the solvent and unreacted materials are recovered, whereby a desired fatty acid amide can be obtained economically. When a di-substituted carbodiimide is used as a dehydrating agent, the reaction can be terminated in a short period of time at a low temperature. Examples of such di-substituted carbodiimides include diphenylcarbodiimide, diisopropylcarbodiimide, dicyclohexylcarbodiimide and the like. Of these, however, dicyclohexylcarbodiimide is most frequently employed. In this case, said fatty acid, said amine and the di-substituted carbodi-imide are dissolved in separate inert solvents respectively, for example, ether, dioxane, tetrahydrofuran, petroleum ether, ligroin, kerosene, n-hexane, cyclohexane, benzene, toluene, xylene, dichloromethane, dichloroethane, chloroform or carbon tetrachloride, and then the three solutions are mixed together with vigorous stirring at room temperature or below, whereby the reaction is substantially complete in several minutes. Ordinarily, however, the mixture is allowed to stand at room temperature for several hours and then the formed di-substituted urea is separated by filtration. The desired amide can be easily obtained in a high yield. The separated di-substituted urea is again converted to the di-substituted carbodiimide and is re-usable.

2. Reaction of a lower alkyl ester of the fatty acid, or a glyceride containing said fatty acid, with the amine: (the lower alkyl ester referred to in the above is an ester containing an alkyl group having one to five carbon atoms):

The two compounds are used in equimolar amounts or either one of them is used in excess. A mixture of them is heated at lO-250 C while removing the eliminated alcohol as much as possible, whereby the reaction is terminated in a period of about 50 hours to several days. If necessary, a solvent such as toluene or xylene may be used in the above reaction, but no solvent is necessary in most cases. The reaction time can be shortened by using a catalytic amount of an alkaline condensing agent such as lithium, sodium or potassium metal, sodium methylate, sodium ethylate, caustic soda, caustic potash, sodium carbonate or potassium carbonate, or an acidic condensing agent such as sodium hydrogen sulfate or boric acid as a catalyst.

3. Reaction of a fatty acid halide with the amine:

This reaction is carried out in the following manner:

The amine is dispersed in water or in an aqueous mixed solvent comprising water and acetone, dioxane or tetrahydrofuran. To the resulting dispersion, the fatty acid halide is gradually added at O-30 C in the presence of an alkali such as caustic soda, caustic potash, sodium carbonate, potassium carbonate or sodium hydrogen carbonate, whereby a desired amide of the present invention can be obtained. Alternatively, the amine is dissolved in an inert organic solvent such as acetone, methylethylketone, methylisobutylketone, ether, dioxane, tetrahydrofuran, petroleum ether, ligroin, kerosene, benzene, toluene, xylene, chloroform or carbon tetrachloride, in the presence of a basic substance such as sodium carbonate, potassium carbonate, caustic soda, caustic potash, or tertiary amine such as trimethylamine, triethylamine, dimethylaniline, diethylaniline, pyridine or lutidine, and the solution is gradually charged with the fatty acid halide at 0-20 C and, if necessary, the reaction mixture is then heated, whereby the desired amide of the present invention can be obtained in an extremely high yield.

4. Reaction of an anhydride of the fatty acid with the amine:

The acid anhydride employed in this reaction is a compound represented by the formula,

wherein R is as defined previously and R is identical with R or is an alkyl or alkoxy group having one to four carbon atoms,

The reaction is carried out in such a manner that a solution of the acid anhydride in an inert solvent is gradually added at 0l00 C to the amine or to a solution thereof in an inert solvent and, if necessary, the mixture may be heated to complete the reaction. The fatty acid formed in the reaction and unreacted fatty acid anhydride can be recovered to reuse, if necessary. In the case of a mixed acid anhydride of fatty acid and lower alkyl forrnate which is obtained by reacting a fatty acid of the formula (11) with, for example, ethyl chloroformate, the reaction can be tenninated extremely quickly and at a low temperature. Such mixed acid anhydride is frequently used for the synthesis of peptides and can be prepared according to, for example, the method disclosed in the Journal of American Chemical Society, Vol. 74, page 676 1952).

The solvent in the above reaction may be toluene, xylene, nhexane, cyclohexane, petroleum ether, ligroin, kerosene, ether, dioxane, tetrahydrofuran, acetone, methylethylketone, methylisobutylketone, chloroform or carbon tetrachloride. The reaction is completed in a period of 20-30 minutes to 2 hours by mixing an organic solvent solution of the mixed acid anhydride with the amine at a temperature within the range of from 20 to 20 C. Ordinarily, however, the mixture is allowed to stand overnight at room temperature to complete the reaction, whereby the desired fatty acid amide of the present invention can be easily obtained.

The fatty acid amides of the present invention have excellent cholesterol-lowering effects, as is clear from the following experimental example showing a comparison in cholesterollower action between known cholesterol-lowering agents and some of the compounds of the present invention. However, the compounds of the present invention are not limited to them.

USE EXAMPLE Variation (1 value of treated group m X V W value of control group The cholesterol pool variations of the test compounds were as shown in Table l, and all of the present compounds showed far more prominent cholesterol-lowering. effects than in the case of the known compounds, B-sitosterol and linoleic acid, despite the fact that they were used in smaller amounts.

TABLE L-CFIOLESTEROL POOL VARIATIONS OF TEST COMPOUNDS Percent Variation Compounds Chemical structures in diet (percent) Linoleoyl-a-(2-thienyl)-ethyl amide O. 2 48 C17H31CONHCH 8/ In actual application of the fatty acid amides of the present invention for lowering cholesterol level in the blood, the compounds are orally administered in a dose about 01-10 g/day. Ordinarily, pharamaceutically acceptable inert carriers may be used for oral administration of the amides.

Alternatively, the fatty acid amides may be incorporated into foodstuffs to give enriched foodstuffs.

Foods into which the said amides may be incorporated in line with the object of the present invention are as follows: dairy products such as butter, margarine, cheese, cream, ice cream, skim milk, dry milk, and whole milk; animal and vegetable edible oils such as frying oils, salad oils, mayonnaise and lard; cereal and related foods such as vermicelli, bread, crackers, biscuits, wheat flour, starch, rice, rice flour, dough, buckwheat flour, and misc (Japanese bean paste); confectioneries such as caramels, chocolate, chewing gum, wheatglutens, and candles; processed meat and fish such as ham, sausages, and pasty products; and other various foods.

Because of their low toxicity, the aforesaid higher unsaturated fatty acid amides can be admixed with the said foods in an extremely wide range of proportion and should be appropriately used depending on the amount and the frequency of intake of the-food to be employed. For example, cream or the like, the intake of which is usually small may contain a higher percentage of the said amides, whereas wheat flour, rice flour or the like, the intake of which is rather large may contain a lower percentage of the said amides. Generally, the range varies from about 0.1 percent to about 80 percent by weight of the enriched foodstuff.

The intake amount of the active ingredient (acid amide) in the foodstuff is preferably about g per day at the maximum.

in admixing or compounding the said amides, there may be added without prejudicially influencing the accomplishment of the present invention other commonly-used additives such as natural or synthetic emulsifying agents for foods (e.g., lecithin, sorbitan, sucrose esters, fatty acid monoglyceridees antioxidants for foods [c.g. BHT, Bl-IA (butylated hydroxyanysole), tocopherlls, propyl gallate, nordihydroguaiaratic acid], coloring agents, flavors, seasonings, and water.

For example, in applying the present invention to margarine, fats such as beef tallow, lard and a hardened oil (cg. hardened corn oil) are admixed with oils such as soybean oil, peanut oil, cotton seed oil and safflower oil in a compounding machine so as to prepare a product of suitable melting point and, to the resulting mixture, there is added an appropriate amount of the above-mentioned amides according to need and the object in view, a coloring agent, aqueous sodium chloride solution, an emulsifying agent, an antioxidant and the like. Then, the resultant mixture is vigorously agitated in an emulsiher at a temperature a little higher than the melting point and rapidly chilled in a chilling machine to obtain enriched margarme.

Since the higher fatty acid amides used in the present invention are extremely soluble in fats, the said amides can be admixed with edible oils and the like by simply agitating the mixture in a compounding machine, if necessary, with slight warming.

Addition to powdered foods such as wheat flour and rice flour may be practiced by mixing the foods and the said amides in a mill or compounding machine. If necessary, the amides may be added in the form of a solution in an inert organic solvent such as ethyl alcohol or a vegetable oil.

Enriched bread, enriched wheat vermicelli, enriched crackers, enriched biscuits, enriched instant Chinese vermicelli and the like may be prepared by, per se, conventional procedures using wheat flour, buckwheat flour or the like previously admixed with the said amides.

According to the present invention enriched rice and the like can be prepared by admixing rice and the like coated with the said amides with untreated rice or by mixing the particles made of the said amides, wheat flour, cellulose acetate, gum arabic, rice powder and the like with untreated rice.

EXAMPLE 1 To a solution of 2.! g of triethylamine and 3.8 g of a-(2- pyridyl)benzlamine in 70 ml of ether, 4 g of linoleoyl chloride was added dropwise at l5-20 C with stirring. The mixture 7 was stirred at room temperature for 2 hours, then allowed to stand for one night, and subsequently refluxed for 2 hours with stirring. After cooling, the reaction mixture was washed with water, an aqueous sodium carbonate solution and then water, and dried over Glaubers salt, and then the solvent was distilled off therefrom. Subsequently, the reaction product was purified by a silica gel column chromatograph with a mixed solvent of benzene and chloroform, and the solvent was completely distilled off to give 7.3 g (yield: 79 percent) of the objective linoleoyl-a-( Z-pyridyl )benzylarnide, N 1.5330.

Elemental analysis Theoretical values cnHnc0NHsH- N Analytical I values 0 (percent).. 80.67 80.67 H (percent).- 9.44 9.48 N (percent)... 6. 11 6. 27

EXAMPLE 2 In a distilling flask, a mixture of i4 g of oleic acid and 12 g of a-(3-pyridyl)benzylamine was heated with stirring in a nitrogen stream at C for 45 hours while removing the water lay-produced from the reaction system. The reaction product was purified by a silica gel column chromatograph with a mixed solvent of benzene and chloroform and the solvent was distilled off completely to give 15.4 g (yield: 71 percent) of the objective oleoyl-a-(3-pyridyl)benzylamide, N 1.5323.

Elemental analysis A mixture of 7 g of isostearic acid, 4 g of a-( 2-thienyl)ethylamine, 0.2 g of p-toluenesulfonic acid in 50 ml of xylene was refluxed for 40 hours while removing the water byproduced from the reaction vessel. After the completion of reaction, 50 ml of ether was added thereto and the reaction mixture was washed in a cooled state with dilute hydrochloric acid, water, an aqueous sodium carbonate solution and water, and then dried over Glaubers salt. The solvent was distilled off completely to give 7.2 g (yield: 73 percent) of the objective isostearoyl-a-(2-thienyl)ethylamide, N 1.5099.

Elemental analysis Theoretical values as nitrogen and infrared absorption spectrum showed an absorption of NH at 3260 cm and an absorption of CON= at 1650 cm. These results indicated that the material was the objective i-C17H35CONHCH Analytical S values CH1 whale oil-C 0 NH GHQ 0 (percent) 73.10 73.28 I H (percent) 11.02 10. 94 N (percent) H- 3.38 3.56 S (percent) 8.00 8.14

N EXAMPLE 4 To a solution of 1.3 g of linolenic acid in 30 ml of ether was EXAMPLE 7 mixed a solution of 0.8 g of a-( 2-thienyl)ethylamine and 1.2 g The temperature of a mixture of 24 g of oleic anhydride and of dicyclohexyl carbodiimide in 20 ml of ether at 0 C with 25 g of a-( 2-pyridyl)benzylamine was gradually raised while stirring. The resultant mixture was stirred for one night. Five stirring the mixture and finally the mixture was stirred at 120 ml of gla i l c i i was added h r n h r l n C for 4 hours. The resultant reaction mixture was washed in a mixtur w llo o Stand f r 2 h r n fil Th filcooled state with an aqueous sodium carbonate solution and mate was'washcd n a c ol at h i te hydr ch oric water, and dried over Glaubers salt, and then the solvent was i water, n aqueous sodium carbonate Solution n w er, distilled off. Subsequently, the resultant reaction product was and then dried over Glaubers salt. The solvent was distilled urified b a ili gel column chromatogra h with a mixed Off c mp y to g g (y l 33 P l ylsolvent of benzene and chloroform and the solvent was y y 0 distilled off completely to give 14.8 g (yield: 75 percent) of the objective oleoyl-a-( 2-pyridyl)benzylamide N 1.5330. Elemental analysis Theoretical values as Elemental analysls Theoretical values as CnHzgCONHCHJ u C11H33CONHGH( Analytical S I values CH 74.58 74.42 N 9. 77 9.56 l 3. 51 3. 62 Analytical S (percent) 8.29 8.27 values g ((percenlg" 83. 83.38

c en 8 EXAMPLE 5 N (Salient). e. 00 6. 24 A mixture of 15 g of methyl linolate and 15 g of a-(Z-thienyl)-phenethylamine was heated at 150 C for 70 hours while EXAMPLE 8 removing by-produced methanol from the reaction vessel. To a solution of 21 g of linoleic acid and 7.7 g of After 'l 100 ml of benzene was added thereto, the triethylamine in 150 ml of toluene was added dropwise 8.4 g resultant f f was washed m cooled State (mum of ethyl chloroformate at -7 C with stirring. After stirring the hydmchlnc acld an aqueous, sodmgzhcarbon'fne solulon and mixture at said temperature for 30 minutes, a solution of 15.5 and due}? over Glauber S Salt e reacuon pro was g of 'a-(2-thienyl)phenethylamine in 70 ml of toluene was 'i p a Smca gel column cilromatograpb and the Solvent added dropwise thereto at -5 to 7 C. The stirring was coni gl 9 'i ar i tinued at said temperature for 20 minutes and then at room z mo eoy ene y am] temperature for 2 hours. The resultant reaction mixture was 0 allowed to stand for one night. Subsequently, the resultant Elemental analysis so reaction mixture was washed in a cooled state with dilute h l 1 hydrochloric acid, water, an aqueous sodium carbonate solu- T gore ma as tion and water. After drying over Glaubers salt and concentrated, to give 23 g (yield: 66 percent) of crystals of the objective linoleoyl-a-(2-thienyl)phenethylamide, m.p. 41 to 42C. C11H31CONHCH\ s i Elemental analysis Analytical Q Theoretical values as values 0,711.10 0 NH 0 H-U C (percent) 77. 23 77. 42 H (percent) 9.10 9.26 N (pereent) 2.93 3.01 s S (percent) 6.67 6.88

Analytical CH2 EXAMPLE 6 Values C A rmxture of 20 g of whale oil and 25 g of ct-(4- H $2323) Z1 Z5? pyridyl)benzylamine was heated at 150 C for hours. After g ggzi g gg: g cooling, 100 ml of ether was added thereto, and the resultant VA p mixture was washed in a cooled state with an aqueous sodium 9 carbonate solution and water, and dried over Glaubers salt. EXAMPLE Thereafter the solvent was completely distilled off. Sub- 70 A mixture of 10 g of safflower oil and 17 g of a-( 2-thienyl)- sequently, the resultant reaction product was purified by a silphenethylamine was heated in a nitrogen stream at 150 C for ica gel column chromatograph with a mixed solvent of hours. After cooling, ml of ether was added thereto. benzene and chloroform and the solvent was distilled off The resultant reaction mixture was washed in a cooled state completely to give 24 g of a material having N 1.5396. with dilute hydrochloric acid, water, an aqueous sodium car- Elementary analysis of the material showed 79.07 percent 75 bonate solution and water, and dried over Glaubers salt, and

of carbon, 6.32 percent of hydrogen and 15.02 percent of then the solvent was distilled off. Subsequently, the resultant solid was the objective objective saflflower oil-C ON HCHlS LHPQ EXAMPLE To a solution of 2.8 g of triethylamine and 3.4 g of a-(2- thienyl)-ethyla.mine in 100 ml of ether, 8 g of linoleoyl chloride was added dropwise at to C with stirring. The resultant mixture was stirred at room temperature for 4 hours, then allowed to stand for one night, and subsequently refluxed for 2 hours. After cooling, the resultant reaction mixture was washed with a cooled aqueous hydrochloric acid, water, an aqueous sodium carbonate solution and water, and dried over Glaubers salt. Thereafter, the solvent was distilled off therefrom. Finally, the solvent was distilled off completely at 80 C under reduced pressure of 0.1 mm Hg, to give 9.0 g (yield: 81 percent) of the objective linoleoyl-a-(2-thienyl)- ethylamide, N 1.5067.

Elemental analysis Theoretical values as Analytical values CH;

0 (percent) 73. 91 74. 04 H (percent) 10. 48 10. 03 N (percent) 3. 47 3. 60 S (percent) 8. 09 8.23

EXAMPLE l 1 Elemental analysis Theoretical values as Analytical values C (percent) 80.48 80. 67 H (percent)... 9. 70 9.48 N (percent) (3. l9 6. 2?

EXAMPLE 12 To a mixture of 1.5 g of triethylamine and 3.0 g of a-(4- pyridyl)-benzylamine in 50 ml of ether, 5.4 g of linoleoyl chloride was added dropwise at 20 to 25 C for 40 minutes with stirring. The resultant reaction mixture was treated by a manner similar to that in Example 1 and there was obtained 5.0 g (yield: 69 percent) of the objective linoleoyl-a44- pyridyl)benzylamide, N 1.5323.

Elemental analysis Theoretical values as Analytical values N 0 (percent) 80. 4!) 80. 67 II (percent). E). 25 ll. 48 N (percentL. 6. 10 b. 27

We claim:

1. A fatty acid amide represented by the formula,

group of the symbol A is methyl.

4. A fatty acid amide according to claim 1, wherein the phenyl lower alkyl of the symbol A is benzyl.

5. A fatty acid amide according to claim 1, wherein the amine moiety is a-(2-thienyl)ethylamine or a-(2-thienyl )phenethylamine,

6. lsostearoyl-a-( Z-thienyl )-ethyl amide.

7. Linoleoyl-a-( 2-thienyl )-ethyl amide.

8. Linoleoyl-a-( 2-thienyl)-phenethyl amide. 

2. Linoleoyl- Alpha -(2-thienyl)-ethyl amide.
 3. A fatty acid amide according to claim 1, wherein the alkyl group of the symbol A is methyl.
 4. A fatty acid amide according to claim 1, wherein the phenyl lower alkyl of the symbol A is benzyl.
 5. A fatty acid amide according to claim 1, wherein the amine moiety is Alpha -(2-thienyl)ethylamine or Alpha -(2-thienyl)phenethylamine,
 6. Isostearoyl- Alpha -(2-thienyl)-ethyl amide.
 7. Linoleoyl- Alpha -(2-thienyl)-ethyl amide.
 8. Linoleoyl- Alpha -(2-thienyl)-phenethyl amide. 